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Saturday, 6 May 2017

Maintaining and Controlling the Blood-Brain Barrier

The blood-brain barrier, or BBB, is a layer of cells that stops specific substances in the blood from entering brain tissue. This is an essential job, since the brain controls our body and keeps us alive. It must be protected from harmful materials. Sometimes, though, researchers are frustrated when a medication that could help a neurological problem is unable to enter the brain due to the presence of the BBB. Understanding how the barrier works and learning how to safely modify its actions are important endeavours.

The Blood-Brain Barrier

The blood-brain barrier consists of tightly packed endothelial cells that line the capillaries around and inside the brain. The membranes of adjacent cells in the barrier are joined by so-called "tight junctions", which block the passage of virtually all materials. Materials are forced to travel through the cells in the barrier in order to enter the brain tissue. This enables the cells to have some control over the passage of the materials.The blood-brain barrier does allow some substances to enter the brain, including nutrients such as oxygen, glucose, amino acids, and water. Brain cells need these chemicals in order to survive. Lipid-soluble substances can also pass through the barrier. Bacteria, other pathogens, and substances that could act as neurotoxins are blocked, however.

Role of an Omega-3 Fatty Acid

Researchers at the Harvard Medical School have recently explored the role of a specific type of omega-3 fatty acid in the blood-brain barrier. Their research has shown that the chemical is important for maintaining the integrity of the BBB and enabling it to block the movement of substances. The fatty acid in question is docosahexaenoic acid, or DHA. It's found in oily fish and certain algae. The researchers have found that the endothelial cells in brain capillaries have two to five times more DHA than the ones in lung capillaries.

The blood-brain barrier protects the brain.

(Public domain photo)

A Transporter Protein

The endothelial cells lining blood vessels around and in the brain contain a protein known as Mfsd2a. This protein transports lipids, or fatty materials, including ones containing DHA. It moves the lipids with DHA into the membrane of the endothelial cells, which keeps the BBB strong. The protein also inhibits transcytosis in the cells. This is a process in which a substance enters a cell via vesicle formation (endocytosis), moves to the opposite membrane of the cell, and then leaves the cell in another vesicle (exocytosis). A vesicle is a small, membranous sac. The cell has other ways to transport materials, but some substances must move through the cell by transcytosis.The Harvard researchers have bred mice with a mutated form of the gene that codes for the Mfsd2a protein. The mutation in the gene causes an altered protein to be produced. The altered protein can no longer transport lipids containing DHA. As a result, the mice develop "leaky" blood-brain barriers which allow the passage of materials that are normally blocked. In addition, the formation of the vesicles needed in transcytosis is no longer inhibited, which also increases the passage of materials. The same results occur when mice lack the Mfsd2a protein entirely.

Human Applications

Assuming that the process discovered in mice works the same way in humans, it might be useful to us. If we could temporarily block the activity of the Mfsd2a protein, we might be able to send medications for treating Alzheimer's disease, brain cancer, strokes, and other conditions into the brain. The problem is that we need to do this without allowing harmful substances into the brain, or at least while limiting their entry. Hopefully we will discover how to do this as we learn more about how the blood-brain barrier works.